The long term objective of this proposal is to determine whether Bowman-Birk Inhibitor (BBI) Concentrate (C), a protease inhibitor extracted from soybeans, can cause regression of oral leukoplakia and whether certain candidate intermediate marker endpoints can predict response by serving as a surrogate for oral leukoplakia. The ultimate goal of this research is to prevent human cancer.
The specific aims are: (1) To conduct a placebo-controlled, double-blind and randomized 6 month phase lib cancer control chemoprevention trial of BBIC in patients with oral leukoplakia. (a) To determine the clinical and histologic response rate of oral leukoplakia to BBIC. (b) To serially measure the effect of BBIC on intermediate marker endpoints (IME). 1) In oral mucosal cells the level of proteolytic activity (PA) and levels of erb-B2 (neu), retinoic acid receptor beta (RAR-beta), bcl-2, and mutant p53 protein will be measured. 2) In tissue biopsies of oral leukoplakia lesions the latter four proteins above will also be measured by immunohistochemistry. 3) In serum, the levels of the protein, neu, will be serially measured. (c) To correlate the clinical and histologic responses of oral leukoplakia to the effect on cellular levels of PA, erb-B2 (neu), RAR-beta, bcl-2, and mutant p53 expression, and serum levels of neu. (d) To determine the individual and group side-effects to BBIC. (2) To follow long term (one year) those patients who achieve a PR or CR afterthe initial 6 months trial Based on the phase Ila and early phase lib results we estimate that about 25-35% of patients completing the 6 months of BBIC will fall in this category. The same parameters outlined for specific aim 1 will be measured. Particular attention will be paid to adherence and toxicity as we eventually wish to use BBIC in the long term setting of second malignancy prevention. All aspects of these phase II IME trials will be carefully monitored for compliance, safety, and toxicity by continuous local evaluation by our NCI-approved Data Safety and Monitoring Board (DSMB) and in concert with the NCI. The results from these studies should provide a substantial biologic and therapeutic rationale for a large Phase III randomized risk reduction trial of head and neck cancer as well as provide impetus for further exploration of these non-toxic group of compounds as chemopreventive agents in humans.
